1. Field of the Invention
The present invention relates, in general, to antibodies. In particular, the present invention relates to antibodies to p40.
2. Background Information
LINE-1 is a mammalian retrotransposon (Fanning, T. G. & Singer, M. F. (1987) Biochim. Biophys. Acta 910:203-212; Hutchison, C. A. et al. (1989) Mobile DNA, Berg, D. E. & Howe, M. M. (eds.) Am. Soc. Microbiol., Washington DC. pp. 593-617; Singer, M. F. et al. (1988) Banbury Report 30: Eukaryotic Transposable Elements as Mutagenic Agents. Cold Spring Harbor Press, New York. pp. 71-78). The human element has an internal RNA polymerase promoter (Swergold G. D. (1990) Mol. Cell. Biol. 10:6718-6729) and two open reading frames, the first of which encodes a protein (p40) of ca. 40 kd with no known function (Skowronski, J. et al. (1988) Mol. Cell. Biol. 8:1385-1397). Human LINE-1 sequences (L1Hs) make up about 5% of the human genome and most are defective, primarily due to truncation and internal rearrangements (Grimaldi, G. et al. (1984) EMBO J. 3:1753-1759). Most full length, unrearranged elements are also defective since they contain open reading frames interrupted by stop codons (Skowronski, J. et al. (1988) Mol. Cell. Biol. 8:1385-1397). Nevertheless, functional (transposable) elements must exist since de novo integrations have been observed in three individuals: in two cases there were integrations into factor VIII genes (Kazazian, H. H. et al. (1988) Nature 332:164-166) and in one case into a c-myc allele (Morse, B. et al. (1988) Nature 333:87-90).
Previous studies have suggested that L1Hs are not active in most cells since specific transcripts were not detected by Northern blotting and/or primer extension (Skowronski, J. & Singer, M. F. (1985) Proc. Natl. Acad. Sci. U.S.A. 82:6050-6054; Skowronski, J. & Singer, M. F. (1986) Cold Spring Harbor Symp. Quant. Biol. 51:457-464). Exceptions were cell lines derived from cancers of epithelial origin; in several cell lines derived from human testicular germ cell tumors (teratocarcinomas) L1Hs-specific RNA and proteins were detected and transcription appeared to be regulated since it was observed only in undifferentiated cells (Skowronski, J. & Singer, M. F. (1985) Proc. Natl. Acad. Sci. U.S.A. 82:6050-6054; Skowronski, J. & Singer, M.F. (1986) Cold Spring Harbor Symp. Quant. Biol. 51:457-464; Skowronski, J. et al. (1988) Mol. Cell. Biol. 8:1385-1397). The exact meaning of these observations is not clear, however, since cell lines may represent minor species present within the tumor mass (Brawn, P. N. (1987) Cancer 59:2042-2046; Loehrer, P. L. et al. (1987) Semin. Oncol. 12:304-316). In addition, cell lines have often been so "massaged" by the experimenter that it may be idealistic to expect that they faithfully reflect the characteristics of their progenitors in the tumor of origin (Andrews, P. W. et al. (1987) Teratocarcinomas and Embryonic Stem Cells. Robertson, E. J. (ed.). IRL Press, Oxford. pp. 207-248). Therefore, the present invention provides antibodies to p40 for examining tumors for L1Hs expression.